The post-synaptic receptor-channel complex is the molecular element which mediates the transduction of a chemical signal into an electrical signal. The precise kinetic relationship of this chemical to electrical transduction has been difficult to determine with a temporal resolution that is relevant for synaptic signalling in the mammalian CNS. The development of a novel rapid "concentration-clamp" in preliminary studies now provides the means to address this problem. Preliminary results suggest that the rates of activation, desensitization, and recovery from desensitization of the glutamate channels are far faster than previously thought. Preliminary studies has also revealed a previously unreported high conductance rapidly desensitizing glutamate channel. This channel has characteristics that strongly suggest it may mediate the fast epsc in much of the mammalian CNS. This grant proposal seeks to more firmly establish the relationship between the rapidly desensitizing glutamate channel and the faster epsc. The identification of this new glutamate channel and its fast kinetic characteristics suggest that the kinetic model of synaptic transmission derived from studies at the cholinergic synapse at the neuromuscular junction may not be applicable for the glutamate synapse in the CNS. This grant proposal seeks to examine an alternate model for describing the kinetics of the signal transduction process at the CNS synapse. Other questions to be addresses during the grant award include: What factors may modulate the kinetics of the different glutamate channels? Are there pharmacologic agents that can differentiate between the low conductance and the high conductance quisqualate channel? are the properties of glutamate channels obtained from neurons in brain slices different from those obtained from cultured or enzyme treated neurons?